Insulin ResistancePhase 4NCT01765946
Metformin and Longevity Genes in Prediabetes
A Phase 4 study testing Metformin in people with Insulin Resistance and Prediabetes, run by University of Padova at 1 site in Italy.
Trial summary
Pre-diabetes, a condition characterized by hyperglycaemia, is associated with increased cardiovascular risk and reduced life expectancy, as compared to the general population. AMP-activated protein kinase (AMPK) is an enzyme that plays a key role in cellular energy homeostasis and metabolism, and recently it has been… Read more about this study
- Who is it for?
- Ages 40 to 75 years
- Conditions the study is for
- Insulin Resistance, Prediabetes, Aging
- What is being tested?
- Metformin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 38 participants
- Where
- 1 siteItaly
- Study dates
- Jun 2010to Mar 2013
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pre-diabetes, defined as IFG (fasting glucose between 100 and 125 mg/dl) or IGT (2h post-oral glucose load (75g) between 140 and 199 mg/dl);
- Age 40-75 years;
- Both genders.
Who cannot join
- Type 1 or 2 diabetes mellitus;
- Pregnancy, lactation;
- Acute, chronic or inflammatory diseases;
- Neoplasms;
- Immunological diseases, organ transplantation, steroid therapy;
- Uncontrolled arterial hypertension (systolic pressure > 180 mmHg or diastolic > 120 mmHg);
- Recent(within 3 months) surgical intervention or cardiovascular accidents;
- Known allergy to metformin.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of Metformin on Longevity Gene Expression and Inflammation and Prediabetic Individuals. A Placebo-controlled Trial
Pre-diabetes, a condition characterized by hyperglycaemia, is associated with increased cardiovascular risk and reduced life expectancy, as compared to the general population. AMP-activated protein kinase (AMPK) is an enzyme that plays a key role in cellular energy homeostasis and metabolism, and recently it has been demonstrated that AMPK regulates aging pathways, as well. AMPK is susceptible to modulation through pharmacologic (e.g. metformin) and non-pharmacologic (e.g. physical exercise) interventions. This clinical trial aims to describe the effects of the AMPK pathway on longevity genes and inflammation in the setting of pre-diabetes in vivo and in vitro. To this end, the investigators will compare treatment with metformin (500 mg t.i.d) for 2 months, versus placebo in pre-diabetic subjects. The investigators will assess expression of longevity genes SIRT1, p66Shc, p53 and mTOR in peripheral blood mononuclear cells (PBMCs) ex vivo. The investigators will evaluate monocyte polarization by flow cytometry, according to the expression of surface antigens (CD68, CCR2, CD163, CD206, CX3CR1) to determine the prevalence of pro- or anti-inflammatory cells. Inflammatory cytokines (TNF-alpha, MCP-1, IL-1, IL-6, IL-10, CCL12) will also be determined. In the in vitro study the investigators will evaluate the effects of AMPK activation or inhibition on longevity gene and protein expression.
- Conditions
- Insulin Resistance, Prediabetes, Aging, Inflammation
- Being tested
- Metformin, placebo
- Keywords
- Insulin resistance, Prediabetes, Longevity genes, Inflammation, Metformin
- Medical subject headings
- Insulin Resistance, Prediabetic State, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Also called Glucophage
Metformin tablets 500 mg tris in die (tid)
placeboDrug
| Study group | Role | What they receive |
|---|---|---|
| Metformin | Experimental | Metformin tablets 500 mg tid for 2 months Receives: Drug: Metformin |
| Placebo | Placebo comparator | Placebo tables tid for 2 months Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Longevity gene expression
Change in the expression of longevity genes Sirtuin-1, p66Shc, mTor, p53 in peripheral blood mononuclear cells (PBMC)
Measured: 2 month after treatment
Secondary outcomes (2)
Insulin sensitivity
A dynamic measure of insulin sensitivity (Si) from the frequently sampled OGTT
Measured: 2 months after treatment
Monocyte polarization status
Polarization of circulating monocytes in M1 (CD68+CCR2+) and M2 (CX3CR1+CD163+/CD206+)
Measured: 2 months after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2013 (estimated)
- Study startJun 2010
- Primary completionMar 2013
- Study completionMar 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Insulin ResistanceStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Padova
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Angelo Avogaro, University of Padova
- Investigators
- Angelo Avogaro, M.D. Ph.D., Principal investigator, University of Padova
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01765946
- Sponsor's protocol ID
- MetAge
- Status last verified
- Mar 2013
- First submitted
- 8 Jan 2013
- Last updated
- 13 Mar 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
de Kreutzenberg SV, Ceolotto G, Cattelan A, Pagnin E, Mazzucato M, Garagnani P, Borelli V, Bacalini MG, Franceschi C, Fadini GP, Avogaro A. Metformin improves putative longevity effectors in peripheral mononuclear cells from subjects with prediabetes. A randomized controlled trial. Nutr Metab Cardiovasc Dis. 2015 Jul;25(7):686-93. doi: 10.1016/j.numecd.2015.03.007. Epub 2015 Mar 24.
PubMed 25921843
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Metformin on Longevity Gene Expression and Inflammation and Prediabetic Individuals. A Placebo-controlled Trial
- ClinicalTrials.gov ID
- NCT01765946
- Acronym / sponsor ID
- MetAge
- Conditions
- Insulin Resistance, Prediabetes, Aging, Inflammation
- Keywords
- Insulin resistance, Prediabetes, Longevity genes, Inflammation, Metformin
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- University of PadovaUniversity, hospital or other
- Study start
- Jun 2010
- Primary completion
- Mar 2013 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 11 Jan 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Pre-diabetes, a condition characterized by hyperglycaemia, is associated with increased cardiovascular risk and reduced life expectancy, as compared to the general population. AMP-activated protein kinase (AMPK) is an enzyme that plays a key role in cellular energy homeostasis and metabolism, and recently it has been demonstrated that AMPK regulates aging pathways, as well. AMPK is susceptible to modulation through pharmacologic (e.g. metformin) and non-pharmacologic (e.g. physical exercise) interventions. This clinical trial aims to describe the effects of the AMPK pathway on longevity genes and inflammation in the setting of pre-diabetes in vivo and in vitro. To this end, the investigators will compare treatment with metformin (500 mg t.i.d) for 2 months, versus placebo in pre-diabetic subjects. The investigators will assess expression of longevity genes SIRT1, p66Shc, p53 and mTOR in peripheral blood mononuclear cells (PBMCs) ex vivo. The investigators will evaluate monocyte polarization by flow cytometry, according to the expression of surface antigens (CD68, CCR2, CD163, CD206, CX3CR1) to determine the prevalence of pro- or anti-inflammatory cells. Inflammatory cytokines (TNF-alpha, MCP-1, IL-1, IL-6, IL-10, CCL12) will also be determined. In the in vitro study the investigators will evaluate the effects of AMPK activation or inhibition on longevity gene and protein expression.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metformin | Experimental | Drug: MetforminMetformin tablets 500 mg tid for 2 months |
| Placebo | Placebo comparator | Drug: placeboPlacebo tables tid for 2 months |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Pre-diabetes, defined as IFG (fasting glucose between 100 and 125 mg/dl) or IGT (2h post-oral glucose load (75g) between 140 and 199 mg/dl);
- Age 40-75 years;
- Both genders.
Key exclusion criteria (8 listed)
- Type 1 or 2 diabetes mellitus;
- Pregnancy, lactation;
- Acute, chronic or inflammatory diseases;
- Neoplasms;
- Immunological diseases, organ transplantation, steroid therapy;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetforminAlso: GlucophageMetformin tablets 500 mg tris in die (tid) | Drug | Metformin |
| placebo | Drug | Placebo |
Primary outcome
Longevity gene expression
Time frame: 2 month after treatment
Change in the expression of longevity genes Sirtuin-1, p66Shc, mTor, p53 in peripheral blood mononuclear cells (PBMC)
2 secondary outcomes
Insulin sensitivity
Time frame: 2 months after treatment
Monocyte polarization status
Time frame: 2 months after treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2013.
- Derived from this study: PubMed 25921843de Kreutzenberg SV, Ceolotto G, Cattelan A, Pagnin E, Mazzucato M, Garagnani P, Borelli V, Bacalini MG, Franceschi C, Fadini GP, Avogaro A. Metformin improves putative longevity effectors in peripheral mononuclear cells from subjects with prediabetes. A randomized controlled trial. Nutr Metab Cardiovasc Dis. 2015 Jul;25(7):686-93. doi: 10.1016/j.numecd.2015.03.007. Epub 2015 Mar 24.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Angelo Avogaro, M.D. Ph.D. principal investigator
University of Padova
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Metformin in people with Insulin Resistance and Prediabetes, run by University of Padova at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Mar 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Longevity gene expression (time frame: 2 month after treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01765946, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2013.